It is generally accepted that anterior pituitary thyrotrophs are under the direct influence of the hypothalamic hormone, thyrotropin releasing hormone (TRH). Thyrotrophs secrets thyrotropin (TSH), which stimulates thyroid gland secretion. This hypothalamic-pituitary-thyroid axis exhibits the classic feedback response observed in other neuro-endocrine systems; systemic thyroid hormone concentration is detected by the thyrotrophs, which respond with TSH secretion that is inversely proportional to thyroid hormone concentration. The exact mechanism by which these "signals" (TRH and thyroid hormone) to the thyrotroph are integrated into a final response (altered TSH secretion) is not clear and is an active area of research interest. In addition, somatostatin (another hypothalamic hormone) and the concentration of TSH already in the blood (short-loop feedback) may affect the profile of TSH secretion. This second hypothalamic hormone, somatosttin, is believed to have a primary physiologic function of regulating growth hormone (GH) secretion from pituitary somatotrophs. This proposed research will examine the secretion of TSH and GH from rat anterior pituitary cells isolated from the complication of a continuously adapting system (i.e., changes in thyroid and TRH secretion be maintaining the cells in a specifically designed dynamic in vitro system. The cells will be continuously superfused with a maintenance media to which agents may be introduced, permitting the determination of the secretion profile over a desired period of time. Specifically, we will examine three areas of current interest: 1. The parameters (concentration and duration) required for TRH-stimulated, and somatostatin-inhibited, pituitary TSH and GH secretion. 2. The dose- and time-dependency of TSH superfusion for the short-loop feedback mechanism for suppression to TSH secretion. 3. Age-related changes in thyrotropin control mechanisms. Pituitaries will be studied in rats of ages neonate to 2 years of age.